Iron Metabolism Contributes to Prognosis in Coronary Artery Disease: Prognostic Value of the Soluble Transferrin Receptor Within the AtheroGene Study

TY - JOUR

T1 - Iron Metabolism Contributes to Prognosis in Coronary Artery Disease: Prognostic Value of the Soluble Transferrin Receptor Within the AtheroGene Study

AU - Weidmann, Henri

AU - Bannasch, Johannes H

AU - Waldeyer, Christoph

AU - Shrivastava, Apurva

AU - Appelbaum, Sebastian

AU - Ojeda-Echevarria, Francisco Miguel

AU - Schnabel, Renate

AU - Lackner, Karl J

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Karakas, Mahir

PY - 2020/5/5

Y1 - 2020/5/5

N2 - Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow-up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11-1.44, P<0.001) after adjustment for sex and age. This association remained significant (HR, 1.23; 95% CI, 1.03-1.46, P=0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs-Tnl), and hemoglobin levels. Conclusions In this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

AB - Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow-up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11-1.44, P<0.001) after adjustment for sex and age. This association remained significant (HR, 1.23; 95% CI, 1.03-1.46, P=0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs-Tnl), and hemoglobin levels. Conclusions In this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

KW - Aged

KW - Biomarkers/blood

KW - Coronary Angiography

KW - Coronary Artery Disease/blood

KW - Female

KW - Germany

KW - Humans

KW - Iron/metabolism

KW - Male

KW - Middle Aged

KW - Myocardial Infarction/blood

KW - Myocardium/metabolism

KW - Predictive Value of Tests

KW - Prognosis

KW - Receptors, Transferrin/blood

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

U2 - 10.1161/JAHA.119.015480

DO - 10.1161/JAHA.119.015480

M3 - SCORING: Journal article

C2 - 32321351

VL - 9

JO - J AM HEART ASSOC

JF - J AM HEART ASSOC

SN - 2047-9980

IS - 9

M1 - e015480

ER -